Potassium-Increasing Regimens in Patients at High Risk of Ventricular Arrhythmias: A Prespecified Observational Analysis of the Randomized POTCAST Trial

BACKGROUND AND AIMS: The POTCAST trial (n=1,200) showed that targeting high-normal plasma potassium levels reduced ventricular arrhythmias in patients with Implantable Cardioverter-Defibrillators (ICDs). We compared changes in plasma potassium and described outcomes across the three regimens used to increase plasma potassium. METHODS: We studied 600 control participants and 572 intervention participants who completed potassium up-titration in POTCAST. Participants in the intervention arm were categorized according to treatment after plasma-potassium up-titration into: a) mineralocorticoid-receptor antagonists (MRAs) monotherapy, b) potassium-supplement monotherapy, or c) combination-therapy with both. The primary endpoint was a composite of sustained ventricular arrhythmia, appropriate ICD-therapy, hospitalization for arrhythmia or heart-failure or all-cause mortality. Safety outcomes included death and electrolyte/renal disturbances. RESULTS: After six months, plasma potassium increased from 4.12 to 4.27 mmol/L (p=0.004) with MRA, from 3.99 to 4.24 mmol/L (p<0.001) with potassium-supplements, and from 3.98 to 4.34 mmol/L (p<0.001) with combination-therapy. The primary endpoint occurred in 29% (n=175) of controls, 22% (n=16) in the MRA group, 21% (n=31) in the potassium-supplements group and in 22% (n=72) in the combination-therapy group (p=0.8 between regimens). Hypokalemia occurred in 13% of controls and in 3%, 9%, and 5% of participants receiving MRA, potassium-supplements and combination-therapy, respectively. Hyperkalemia occurred in 0.2% of controls and in 0%, 3%, and 4% of participants receiving MRA, potassium-supplements, and combination-therapy (p>0.1 between regimens). CONCLUSIONS: Treatment with MRA, potassium-supplements or both increased potassium levels. All regimens were associated with numerically lower endpoint rates than controls. We detected no statistically significant differences in endpoints or safety between regimens.